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STEM I

In STEM class, each student works on developing an independent research project that solves any present issue, or answers any scientific question where the answer is not well known yet. Though each of our projects are different, like our other classes, we spend a lot of time peer editing and helping our classmates better their projects.

My project was focused on finding a way to enhance the hearing of deaf individuals suffering from sensorineural hearing loss, which is a loss of hearing due to damaged hair cells in the inner ear. In my research I looked at different genes and their effects on mechanosensation, which is an integral part of hearing. Through research I found that a certain membrane protein, SID-1, aided cells in RNA inteference. Graphical Abstract

Millions of individuals across the globe suffer from sensorineural hearing loss. A low count of the hair cells in the inner ear results in this hindered hearing ability, due to a reduced number of mechanoreceptors sending signals to the brain from the ear. Hair cells are microscopic mechanoreceptors that are able to transduce sound waves that physically move them, into electrical signals that are then sent to the central nervous system. The mechanoreceptors of Caenorhabditis elegans, or C. elegans, function in a similar manner, and are unable to regenerate after the larvae stage. During mechanotransduction, a key component is the sid-1 gene in C. elegans which enhances neuronal RNAi, and if utilized correctly, could potentially enhance mechanotransduction itself. In this study, two groups of C elegans, a N2 strain as well as a sid-1 strain were used. The functionality of the C. elegans’ mechanoreceptors in each group were tested through nose touch assessments. C. elegans in the wildtype group had a lower response to the gentle touch and harsh touch assessments than C. elegans in the sid-1 group. A heightened response from C. elegans lacking the sid-1 gene implied that the gene was successfully able to enhance the functionality of the existing mechanoreceptors on the C. elegans. Using methods found in gene therapy, such as adeno-associated viruses, enhancing the gene could be practiced on non-hearing individuals to allow for heightened hearing abilities.

Research Proposal

Problem: The effects of damaged hair cells are irreversable.

Solution: Using gene editing, the function of hair cells could be restored

Background

Sensorineural hearing loss causes deafness in many individuals across the globe.This specific type of hearing loss is caused by damaged sensory receptors called hair cells. In C. elegans, the SID-1 transmembrane protein is known to enhance neuronal RNA interference (RNAi) and silence genes with locally expressed dsRNA (Calixto et al., 2010). In humans, SID-1 could potentially help damaged hair cells function.

Methods Infographic Cleggin GT HT

Takeaways

The SID-1 transmembrane protein may have an impact on mechanosensation. in C. elegans. During the gentle touch assessment, the SID-1 group almost reached their maximum speeds, and continued reacting at those speeds during the harsh touch simulation.

Future Extension

Possible extensions of this work include using adeno-associated viruses to induce SID-1 creation (Tao et al., 2022), or testing the difference in levels of SID-1 in hearing and deaf individuals.

References

Calixto, A., Chelur, D., Topalidou, I., Chen, X., & Chalfie, M. (2010). Enhanced neuronal RNAi in C. elegans using SID-1. Nature methods, 7(7), 554–559. https://doi.org/10.1038/nmeth.1463

McClanahan, P. D., Xu, J. H., & Fang-Yen, C. (2017). Comparing Caenorhabditis elegans gentle and harsh touch response behavior using a multiplexed hydraulic microfluidic device. Integrative biology : quantitative biosciences from nano to macro, 9(10), 800–809. https://doi.org/10.1039/c7ib00120g

Tao, Y., Liu, X., Yang, L., Chu, C., Tan, F., Yu, Z., Ke, J., Li, X., Zheng, X., Zhao, X., Qi, J., Lin, C. P., Chai, R., Zhong, G., & Wu, H. (2022). AAV-ie-K558R mediated cochlear gene therapy and hair cell regeneration. Signal Transduction and Targeted Therapy, 7(1). https://doi.org/10.1038/s41392-022-00938-8